IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15140-z.html
   My bibliography  Save this article

2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

Author

Listed:
  • Carole Trzaska

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

  • Séverine Amand

    (UMR 7245 CNRS-MNHN)

  • Christine Bailly

    (UMR 7245 CNRS-MNHN)

  • Catherine Leroy

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

  • Virginie Marchand

    (UMS2008 IBSLor CNRS-Université de Lorraine-INSERM)

  • Evelyne Duvernois-Berthet

    (UMR7221 CNRS-MNHN)

  • Jean-Michel Saliou

    (University of Lille)

  • Hana Benhabiles

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

  • Elisabeth Werkmeister

    (Cellular Microbiology and Physics of Infection Group, Center for Infection and Immunity of Lille, CNRS UMR8204, INSERM U1019, Institut Pasteur de Lille, Lille Regional Univ. Hosp. Centr., Lille Univ.)

  • Thierry Chassat

    (Institut Pasteur de Lille – PLEHTA (Plateforme d’expérimentation et de Haute Technologie Animale))

  • Romain Guilbert

    (Institut Pasteur de Lille – PLEHTA (Plateforme d’expérimentation et de Haute Technologie Animale))

  • David Hannebique

    (Institut Pasteur de Lille – PLEHTA (Plateforme d’expérimentation et de Haute Technologie Animale))

  • Anthony Mouray

    (Institut Pasteur de Lille – PLEHTA (Plateforme d’expérimentation et de Haute Technologie Animale))

  • Marie-Christine Copin

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

  • Pierre-Arthur Moreau

    (LGCgE, Laboratoire de Génie Civil et géo-Environnement)

  • Eric Adriaenssens

    (CANTHER – Cancer Heterogeneity, Plasticity and Résistance to Therapies)

  • Andreas Kulozik

    (EMBL/Medical Faculty Molecular Medicine Partnership Unit)

  • Eric Westhof

    (Institute of Molecular and Cellular Biology of the CNRS UPR9002/University of Strasbourg)

  • David Tulasne

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

  • Yuri Motorin

    (CNRS - Université de Lorraine)

  • Sylvie Rebuffat

    (UMR 7245 CNRS-MNHN)

  • Fabrice Lejeune

    (CANTHER – Cancer Heterogeneity, Plasticity and Resistance to Therapies)

Abstract

Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently shown high-efficiency correction of UGA and UAA nonsense mutations. One active constituent of this extract is 2,6-diaminopurine (DAP). In Calu-6 cancer cells, in which TP53 gene has a UGA nonsense mutation, DAP treatment increases p53 level. It also decreases the growth of tumors arising from Calu-6 cells injected into immunodeficient nude mice. DAP acts by interfering with the activity of a tRNA-specific 2′-O-methyltransferase (FTSJ1) responsible for cytosine 34 modification in tRNATrp. Low-toxicity and high-efficiency UGA nonsense mutation correction make DAP a good candidate for the development of treatments for genetic diseases caused by nonsense mutations.

Suggested Citation

  • Carole Trzaska & Séverine Amand & Christine Bailly & Catherine Leroy & Virginie Marchand & Evelyne Duvernois-Berthet & Jean-Michel Saliou & Hana Benhabiles & Elisabeth Werkmeister & Thierry Chassat & , 2020. "2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15140-z
    DOI: 10.1038/s41467-020-15140-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15140-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15140-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15140-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.